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1.
Cancer Detect Prev ; 19(4): 374-80, 1995.
Article in English | MEDLINE | ID: mdl-7553680

ABSTRACT

Since 1974, and as of March, 1993, we have used T/Tn antigen vaccine in safe, specific, effective, long-term intradermal vaccination against recurrence of advanced breast carcinoma (CA). Staging is by the pathologic TNM system. Treatment is ad infinitum. Of 19 consecutive breast carcinoma patients vaccinated, six Stage IV, six Stage III, and seven Stage II all survived > 5 years postoperatively. Three Stage III, three Stage IV, and five Stage II patients (i.e., 11) survived > 10 to > 18 years. Five others are alive but have not reached 10 years; three of them have no evidence of disease (NED). Three patients died of CA before reaching 10 years. An additional three breast CA patients are being treated for > 2 years, but, < 5 years postoperatively, they are NED. The vaccination are presented as a delayed-type hypersensitivity reaction with significant inflammation with increase of helper T lymphocytes and decrease of T suppressor/cytotoxic cell ratio.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/administration & dosage , Antigens, Viral, Tumor/administration & dosage , Breast Neoplasms/prevention & control , Vaccines/administration & dosage , Breast Neoplasms/immunology , Breast Neoplasms/pathology , Female , Humans , Hypersensitivity, Delayed/immunology , Injections, Intradermal , Neoplasm Staging , Recurrence , Retrospective Studies , Survival Rate
2.
Cancer Detect Prev ; 19(2): 173-82, 1995.
Article in English | MEDLINE | ID: mdl-7750105

ABSTRACT

Pathogenetic aspects of pancarcinoma T/Tn autoantigens were investigated; they are present in approximately 90% of all carcinomas from incipience and throughout. T/Tn are occluded in noncarcinoma (non-CA) diseased and healthy tissues. By serological and immunohistochemical methods, we found that well-differentiated carcinomata express a higher proportion of T than Tn, while in poorly differentiated carcinomata, Tn predominates over T. Tn density of primary carcinomas correlates positively with aggressiveness, early clinical relapse, and early death. Delayed-type skin hypersensitivity to T (DTHR-T) and solid-phase anti-T antibody immunoassay (SPIA-T), respectively, detected 85% of 461 and 88% of 222 carcinoma patients; < 7% of over 450 benign diseased and healthy subjects reacted positively in these assays. T/anti-T assays are highly effective in detecting incipient (TisN0M0 and T1N0M0) carcinomas: DTHR-T-85% of 41, and SPIA-T-96% of 26 patients. Positive anti-T tests predicted CA in 74% of 47 patients months to years before their biopsy/X-ray turned positive.


Subject(s)
Antigens, Neoplasm/analysis , Antigens, Tumor-Associated, Carbohydrate/analysis , Autoantigens/immunology , Carcinoma/diagnosis , Adenocarcinoma/diagnosis , Adenocarcinoma/immunology , Antibodies/blood , Breast Neoplasms/diagnosis , Breast Neoplasms/immunology , Carcinoma/immunology , Carcinoma, Ductal, Breast/diagnosis , Carcinoma, Ductal, Breast/immunology , Case-Control Studies , Cohort Studies , Humans , Immunoglobulin M/blood , Isoantigens/immunology , Prognosis
3.
Cancer Biother ; 9(1): 7-15, 1994.
Article in English | MEDLINE | ID: mdl-7812359

ABSTRACT

For nearly 20 yrs, we used T/Tn antigen vaccine in safe, specific, effective, long-term intradermal vaccination against recurrence of advanced breast carcinoma. Treatment is ad infinitum. All 18 breast carcinoma patients treated, pTNM Stages IV (6), III (6), and II (6), survived > 5 yrs postoperatively; 10 survived > 10 to > 18 yrs; of the latter, three patients each are Stages III and IV. Five additional 5 yr survivors have not yet reached 10 yrs. The probability that our survival results are due to chance, with NCI "1991 Standard PDQ Data" as control, for all three stages taken together is: 5-yr survival: p < 1 x 10(-8); 10-yr survival: p < 1 x 10(-5). There were no untoward side effects. The vaccination area presented as a delayed-type hypersensitivity reaction, but at variance with the PPD reaction, with significant inflammation, increase of helper T lymphocytes and decrease of the T suppressor/cytotoxic cell ratio.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate/therapeutic use , Breast Neoplasms/therapy , Neoplasm Metastasis/prevention & control , Neoplasm Recurrence, Local/prevention & control , Vaccination , Vaccines , Adult , Breast Neoplasms/immunology , Breast Neoplasms/mortality , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Combined Modality Therapy , Female , Humans , Hypersensitivity, Delayed/immunology , Middle Aged , Neoplasm Staging , Pilot Projects , Survival Rate , Treatment Outcome
6.
Carbohydr Res ; 178: 271-92, 1988 Jul 15.
Article in English | MEDLINE | ID: mdl-3056614

ABSTRACT

In contrast to healthy and noncarcinoma-diseased tissues, greater than 80% of all carcinomas (CAs) tested express immunoreactive O-(2-acetamido-2-deoxy-alpha-D-galacto-pyranosyl)-(1----3)-serine/threon ine [alpha-D-GalpNAc-(1----3)-Ser/Thr] in their glycoproteins. CA cells shed, into the tumor's environment, Tn, which is involved in cancer pathogenesis as adhesion molecule and as autoimmunogen. An increase in density of Tn on primary CA frequently parallels augmented CA aggressiveness. Tn-Active glycoproteins of culture-grown human breast CA DU 4475 cells were isolated from cytoplasm and from spent growth medium, and erythrocyte (RBC) Tn antigen was prepared by (1----3)-beta-D-galactosidase treatment of isolated human O RBC MN glycoprotein-derived Thomsen-Friedenreich (T) antigen. Immunochemical, serological, physical, and chemical analyses showed close resemblance of CA- and RBC-derived Tn antigens. The preponderant carbohydrate in both Tn glycoproteins is the alpha-D-GalpNAc residue, and the antigens have a qualitatively and quantitatively similar amino acid composition. Highly specific rodent monoclonal (Mo) anti-Tn antibodies (Abs) were elicited with Tn RBC and normal O RBC-derived Tn antigen, and compared with CA-anti-Tn MoAbs unwittingly evoked by others. A sensitive enzyme immunoassay (EIA) with Tn antigen as solid phase was developed. In this system, highly purified, "naturally occurring" anti-Tn antibodies, which all humans possess, were more sensitive in quantitating breast CA Tn structures than the anti-Tn MoAbs induced by Tn RBCs, and by RBC- and CA-derived Tn-active antigens. The sensitivity of anti-Tn MoAbs was higher in detecting RBC-Tn.


Subject(s)
Antibodies, Monoclonal , Antibodies , Antigens, Neoplasm/analysis , Antigens, Tumor-Associated, Carbohydrate , Breast Neoplasms/analysis , Erythrocytes/analysis , Amino Acids/analysis , Carbohydrates/analysis , Cell Line , Electrophoresis, Polyacrylamide Gel , Humans , Immunoenzyme Techniques
9.
Cancer ; 55(3): 561-9, 1985 Feb 01.
Article in English | MEDLINE | ID: mdl-2981150

ABSTRACT

Tn antigen is the immediate precursor of the carcinoma (CA)-associated T antigen; both are masked in non-CA tissues. Tn antigen was detected by absorption of human anti-Tn antibody in 46 of 50 primary breast CAs and in all 6 metastases originating from Tn-positive primary CAs. Thirteen of 25 (52%) anaplastic CAs, but only 2 of 15 (13%) well differentiated CAs had more Tn than T; 1 anaplastic CA had neither antigen. Eighteen of 20 benign breast lesions had no Tn; the 2 positive lesions were premalignant. All 19 breast CAs, studied immunohistochemically, reacted strongly with human polyclonal anti-Tn; benign or normal glandular tissues had minimal or no reactivity. Among live cancer cell lines, the most malignant sublines had more Tn than T on their cell surfaces. Preliminary studies with rodent monoclonal anti-Tn and anti-T antibodies gave immunohistochemical reactivity patterns similar to those of the polyclonal antibodies, but the former were less sensitive in absorption tests. Tn is a CA marker that promises to be useful in tumor detection.


Subject(s)
Antigens, Neoplasm/immunology , Antigens, Tumor-Associated, Carbohydrate , Blood Group Antigens/immunology , Breast Neoplasms/immunology , Carcinoma/immunology , Animals , Antibodies, Monoclonal/immunology , Antigen-Antibody Reactions , Antigens, Viral, Tumor/immunology , Carcinoma, Intraductal, Noninfiltrating/immunology , Cell Line , Female , Hemagglutination Tests , Histocytochemistry , Humans , Immunochemistry , Immunosorbent Techniques , Lymphoma/immunology , Mammary Neoplasms, Experimental/immunology , Mice , Neoplasm Metastasis , Neoplasm Recurrence, Local , Rats
10.
Cancer Detect Prev ; 8(1-2): 95-100, 1985.
Article in English | MEDLINE | ID: mdl-4064056

ABSTRACT

We measured the cellular and humoral autoimmune response to carcinoma (CA)-associated T antigen in patients with the earliest clinical stages of lung (T1N0M0) and breast (Tis) CA. We used desialylated MN glycoprotein from healthy human erythrocytes in a single measurement of 1) delayed-type skin hypersensitivity response (DTHR-T) and 2) humoral anti-T response with a solid-phase immunoassay (SPIA-T). DTHR-T detected 19/20 lung CA and 10/12 ductal and 7/10 lobular breast CA patients. Sixteen of 18 stage T1N0M0 lung CA patients had a positive SPIA-T as did 7/8 patients with Tis breast CA. Two of 35 patients with benign lung and 11/144 with benign breast disease had a positive DTHR-T. None of 160 persons with either other non-CA diseases or healthy had a positive DTHR-T. Three of 68 such control subjects had a positive SPIA-T. The difference between CA patients and control populations is statistically highly significant.


Subject(s)
Antigens, Tumor-Associated, Carbohydrate , Breast Neoplasms/immunology , Carcinoma/immunology , Disaccharides/analysis , Lung Neoplasms/immunology , Breast Neoplasms/diagnosis , Female , Humans , Hypersensitivity, Delayed , Lung Neoplasms/diagnosis
12.
J Surg Res ; 35(4): 293-7, 1983 Oct.
Article in English | MEDLINE | ID: mdl-6621025

ABSTRACT

The delayed-type hypersensitivity skin reaction to human erythrocyte-derived Thomsen-Friedenreich (T) antigen was studied in 40 patients with pancreatic disease and in 158 control subjects and its sensitivity and specificity were compared with the carcinoembryonic antigen (CEA) blood levels. The skin reaction to T was positive in 22 of 25 patients with biopsy-proven adenocarcinoma of the pancreas (sensitivity, 88%). In these patients, the CEA levels were elevated above 3.5 ng/ml in 12 of 23 (52%). The skin test to T antigen was negative in 11 of 12 patients with chronic pancreatitis (specificity, 92%), but CEA levels were normal in only five of nine with pancreatitis (56%). Two of the patients with pancreatic carcinoma and one of those with pancreatitis were anergic to mumps and dermatophytin antigens and had thus an invalid skin test. The positive response rate to T antigen was significantly greater (P less than 0.005) in the cancer group than the group with pancreatitis; the CEA response was not significantly different. There were no positive responses to T in 82 healthy volunteers. Among 76 patients with chronic disease including six with malignant tumors of the mesoderm and central nervous system, there were four positive responses: two in heavy smokers and two in patients with chronic lung infection. The specificity of the test overall in 158 controls was thus 97.5%.


Subject(s)
Adenocarcinoma/immunology , Antigens, Tumor-Associated, Carbohydrate , Disaccharides/immunology , Hypersensitivity, Delayed , Pancreatic Neoplasms/immunology , Adult , Aged , Carcinoembryonic Antigen/analysis , Chronic Disease , Female , Humans , Male , Middle Aged , Pancreatitis/immunology
16.
Klin Wochenschr ; 60(3): 121-31, 1982 Feb 01.
Article in English | MEDLINE | ID: mdl-6176752

ABSTRACT

We report here sensitive and specific measurement of immune responses of patients with certain kinds of carcinoma toward the physically and chemically well defined T antigen isolated from healthy human erythrocytes. Over 90% of adenocarcinoma tissues tested possess T-specific immunoreactive structures as determined with human antisera, in contrast to healthy tissues and benign lesions. Adenocarcinoma patients recognize the carcinoma-associated T antigen as foreign. Delayed-type skin hypersensitivity reaction to T antigen (DTHR-T) was positive in all 25 lung adenocarcinoma patients tested, in 88% of 101 patients with ductal, in 43% of 30 patients with lobular or tubular breast carcinoma and in 9/9 patients with adenocarcinoma of body cavities. Patients of all Stages reacted positively. All 7 patients with small cell lung carcinoma and 3/5 with malignant melanoma had a positive DTHR-T. None of 17 patients with malignant brain tumors, leukemia or Hodgkin's disease, sarcoma or thyroid carcinoma reacted. The DTHR-T was specific in that all 77 healthy persons and 48/49 with other diseases, including 23/24 with non-cancer lung disease were negative; one patient with organizing interstitial pneumonitis was positive. This points to a possible source of false positive reactions. 91% of 149 patients with histologically benign breast disease had a negative DTHR-T; the histology of some of the positive ones was reexamined, 2 proved to have carcinoma in situ.


Subject(s)
Antibody Formation , Breast Neoplasms/immunology , Epitopes , Lung Neoplasms/immunology , Adenocarcinoma/immunology , Adolescent , Adult , Aged , Carcinoma, Small Cell/immunology , Child , Erythrocytes/immunology , Female , Humans , Hypersensitivity, Delayed/immunology , Male , Melanoma/immunology , Middle Aged , Skin Tests
18.
Br J Haematol ; 47(3): 453-60, 1981 Mar.
Article in English | MEDLINE | ID: mdl-7006674

ABSTRACT

Interest in anti-Thomsen-Friedenreich (T) antibodies has increased because of their significance in detection of and their possible interaction with human adenocarcinoma. The origin of anti-T, which all humans possess, has not been ascertained. We determined here that anti-T and -Tn agglutinins could readily be induced via the physiological intestinal route by an enteric bacterium, E. coli O86, which possesses T and Tn activities. One dose of live E. coli O86 given in the drinking water to germfree chicks, who had no anti-T and -Tn antibodies, resulted, in all birds, in formation of saline agglutinating anti-T and -Tn antibodies as well as those detectable only by indirect agglutination. Antibody specificity was confirmed by adsorption on and elution from homologous human erythrocytes and for anti-T also by haemagglutination inhibition. In contrast, control chicks raised under ordinary conditions did have anti-T and -Tn prior to feeding E. coli O86. In humans, six diarrhoeic and five healthy infants and the majority of 13 adults investigated were fed killed rather than live E. coli O86. All infants, but one, suffering from diarrhoea showed a significant increase (greater than or equal to 4-fold) in anti-T and/or anti-Tn antibodies; in some, these antibodies were elicited de novo. All four adults with intestinal lesions had a significant increase of anti-T and/or -Tn subsequent to ingestion of E. coli O86, as did five of nine healthy adults, but to a lesser extent. These findings support the immune nature of demonstrable levels of anti-T and -Tn.


Subject(s)
Agglutinins/immunology , Adult , Animals , Antibodies, Bacterial/immunology , Antibody Specificity , Chickens , Escherichia coli/immunology , Escherichia coli Infections/immunology , Female , Hemagglutination Inhibition Tests , Humans , Infant , Male
20.
Immunol Commun ; 10(2): 157-71, 1981.
Article in English | MEDLINE | ID: mdl-6169631

ABSTRACT

Terminal beta-D-galactopyranosyl (Gal) groups are implied in blood group N but not M specificity by the following findings: (a) Rabbit anti-asialoganglioside sera specific for terminal beta-Gal-(1 leads to 3)-GalNac agglutinate human group 0 M and N erythrocytes, the latter to a significantly higher titer, while rabbit anti-ganglioside GMl sera, whereas sialic acid modifies the antibody specificity, do not. The agglutination score with N erythrocytes was about twice that with M red blood cells. The asialoganglioside antibodies were readily absorbed by group 0 N erythrocytes, which were up to 10 times more efficient than group 0 M erythrocytes. Erythrocyte agglutination by the anti-asialoganglioside sera was inhibited by M and N antigen preparations isolated from group 0 red cells ghosts. N antigen was a better inhibitor. Asialoganglioside effectively inhibited the red cell agglutinations by anti-asialoganglioside serum. Ganglioside GMl did not inhibit. (b) Horse anti-pneumococcus Type XIV serum, which has anti-beta-Gal specificity, precipitated highly active N but not M substances. This precipitation was specifically inhibitable by oligosaccharides with terminal beta-Gal. (c) Beta galactosidase specifically inactivated native N and "acid-produced' N substances with the release of about three moles Gal per subunit of N antigen. It did not affect M antigen.


Subject(s)
Carbohydrates/immunology , Epitopes , MNSs Blood-Group System/immunology , Absorption , Animals , Cattle , Chemical Precipitation , Glycosphingolipids/immunology , Hemagglutination Tests , Horses , Humans , Immune Sera/pharmacology , Rabbits , beta-Galactosidase/pharmacology
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